Quercetin

Quercetin is a naturally occurring flavonoid abundant in various fruits and vegetables, known for antioxidant, anti-inflammatory, anti-apoptotic and anti-fibrotic properties. ^[1] It is among the most ubiquitous polyphenols in fruit and vegetables, with onion known to contain the highest quantity. ^{[2] [3]} Quercetin is widely used for its potent antioxidant activity, with effects reported on glutathione, enzymatic activity, signal transduction pathways, and reactive oxygen species. ^[4]

Quercetin has a wide range of biological actions including anti-inflammatory activity, as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. ^[5] One extensively explored mechanism in aging-related disease is activation of sirtuin 1 (SIRT1), through which quercetin is proposed to regulate oxidative stress, inflammatory response, mitochondrial function, autophagy and apoptosis. ^[6] As a senolytic, quercetin was among the first such drugs discovered using a hypothesis-driven approach, transiently disabling the anti-apoptotic pathways that allow senescent cells to survive. ^[7]

In preclinical models the senolytic combination of dasatinib and quercetin is used to eliminate senescent cells, and early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans. ^{[7] [8]} Senolytic clinical trials for conditions including diabetes, idiopathic pulmonary fibrosis and Alzheimer's disease are underway or beginning, and until such studies are done it is too early for senolytics to be used outside of clinical trials. ^[7] A meta-analysis of randomized controlled trials found that quercetin supplementation showed moderate- to high-quality evidence for reducing cardiovascular disease risk factors. ^[9]

Quercetin is reported to play a role in the prevention of age-related disorders including neurodegeneration, diabetes, cancer and inflammation. ^[3] The optimal dose reported to lower blood pressure and inflammation is 500 mg of the aglycone form, though a lower dose from plant sources could be effective given higher bioavailability. ^[2] Adverse effects following supplemental quercetin intake have rarely been reported and have been mild, but adequate safety data for long-term use beyond 12 weeks at high doses of 1000 mg or more are currently not available. ^[12]